1. Field of the Invention
Disclosed are aromatic, alkyl, bicyclic and cycloalkyl amines. These compounds are useful pharmaceutical agents in treating head injury, spinal cord trauma, stroke and a number of other related injuries and conditions.
2. Description of the Related Art
The non-amine portion of some of the aromatic amines (I) are known.
The non-amine portions of the alkyl amines (II) are known to those skilled in the art or can readily be prepared from known compounds by methods known to those skilled in the art.
The non-amine portions of the bicyclic amines (III) are known to those skilled in the art. See, in particular, U.S. Pat. Nos. 3,947,473, 4,003,919, 4,018,799, 4,026,907 and 4,681,890. See also British Patent 947,885 and Chem. Abst., 60, 11991 (1964). EP 202,580-A discloses 3,4-dihydrobenzopyran derivatives, similar to the non-amine portion of the bicyclic amines (III), which are attached to a 4-phenylmethyl-1-piperazinyl or a 4-(4-pyridinylmethyl)-1-piperazinyl group. While these compounds are similar to the bicyclic amines (III) of the present invention, the bicyclic amines (III) do not have a methylene group between the phenyl or 4-pyridinyl substituent and the piperazinyl group.
The non-amine portions of the cycloalkyl amines (IV) are known to those skilled in the art or can readily be prepared from known compounds by methods known to those skilled in the art.
The non-amine portions of the aromatic bicyclic amines (V) are known to those skilled in the art. See, in particular, U.S. Pat. Nos. 4,181,665 (isochromans--6 member heterocyclic ring) and 4,153,612 (2-benzoxepins--7 member heterocyclic ring). These patents also disclose the non-amine portion of the aromatic bicyclic amines (V), attached to various amines, but different amines than included within the present invention. Those amines were disclosed as possessing antihypertensive and tranquilization activity including antidepressant and antianxiety effects. The activity of the aromatic bicyclic amines (V) is quite different.
Published PCT patent application Ser. No. U.S. 86/01797, International Disclosure Number WO87/01706 (PCT 86/01797) discloses amino steroids where the amine portion includes acyclic, aromatic and heterocyclic amine functionality very similar to the amino substituents, where M is --NR.sub.A R.sub.B, of the present invention. In PCT 86/01797, the amino substituent was attached to the terminal carbon atom of the C.sub.17 side chain of a steroid. The present invention differs from PCT 86/01797 in that the non-amine portion is not a steroid. PCT 86/01797 also disclosed numerous references involving various amines and amino substituents which are incorporated here by reference. PCT 86/01797 is the reference which discloses amino substituents most similar to those of the present invention.
The non-amine portion of the hydroquinones (VI) and quinones (VII) are well known to those skilled in the art. Great Britin patent 2,127,814A disloses amino-quinones containing a fused ring containing a nitrogen atom, the hydroquinones (VI) and quinones (VII) of the present patent do not contain a ring fused to the hydroquinone or quinone. J6 1,254,546A discolses acyclic amine quinone derivatives which contain only a simple nitrogen atom in a long side chain of carbon atoms. U.S. Patent discloses amino-quinones but of an indole type.
The non-amine portion of the amino ethers (VIII) are known to those skilled in the art. JA-7,124,369 discloses heptatrienes which are not similar to the bicyclic aromatic/7-member nitrogen-oxygen containing ring system of the amino ethers (VIII)
The non-amine portion of the bicyclic amino ethers (IX) are known to those skilled in the art. EP 244018-A discloses oxazoleamine derivatives but where the oxazole ring is not fused to a phenyl ring as in the present situation. EP 199400-A discloses a fused oxazole-phenyl ring system having a side chain containing nitrogen.
U.S. Pat. No. 4,728,650 (EP 202,580-A) discloses 3,4-dihydrobenzopyran derivatives which are similar to some of the bicyclic amines of formula (III). The activity (utility) of the compounds disclosed in U.S. Pat. No. 4,728,650 is anti-peptic ulcer, antitussive and/or expectorant. The utility claimed for these agents in the present patent application has nothing to do with gastritis caused by inflammation of the gastric mucosa.
Published PCT patent application Ser. No. JP87/00106, International Disclosure Number WO87/05020 (PCT 87/00106) discloses 3,4-dihydrobenzopyrans linked to nitrogen containing heterocyclic groups including 1-piperazinyl substituted in the 4-position with with a variety of nitrogen groups including 4-pyridinylcarbonyl (4-nicotinoyl), and 3-pyridinylmethyl which are similar to some of the bicyclic amines of formula (III).